Roziahanim Mahmud

Antioxidant and antiangiogenic activities of the essential oils of Myristica fragrans and Morinda citrifolia

OBJECTIVE Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans (M. fragrans) (nutmeg) and Morinda citrifolia (M. citrifolia)(mengkudu) oils. METHODS The nutmeg and megkudu essential oils were obtained by steam distillation. The antioxidant activities of both essential oils were determined by beta-carotene/linoleic acid bleaching assay and reducing power while the anti-angiogenic activity was investigated using rat aortic ring assay using various concentrations. RESULTS The results showed that nutmeg oil has higher antioxidant activity than mengkudu oil. The nutmeg oil effectively inhibited the oxidation of linoleic acid with (88.68±0.1)% while the inhibition percentage of oxidation of linoleic acid of the mengkudu oil is (69.44±0.4)%. The nutmeg oil and mengkudu oil showed reducing power with an EC(50) value of 181.4 μg/mL and 3 043.0 μg/mL, respectively. The antiangiogenic activity of nutmeg oil showed significant antiangiogenic activity with IC(50) of 77.64 μg/mL comparing to mengkudu oil which exhibits IC(50) of 109.30 μg/mL. CONCLUSIONS Bioactive compound(s) will be isolated from the nutmeg essential oil to be developed as antiangiogenic drugs.

Bioassay-Guided Antidiabetic Study of Phaleria macrocarpa Fruit Extract

An earlier anti-hyperglycemic study with serial crude extracts of Phaleria macrocarpa (PM) fruit indicated methanol extract (ME) as the most effective. In the present investigation, the methanol extract was further fractionated to obtain chloroform (CF), ethyl acetate (EAF), n-butanol (NBF) and aqueous (AF) fractions, which were tested for antidiabetic activity. The NBF reduced blood glucose (p < 0.05) 15 min after administration, in an intraperitoneal glucose tolerance test (IPGTT) similar to metformin. Moreover, it lowered blood glucose in diabetic rats by 66.67% (p < 0.05), similar to metformin (51.11%), glibenclamide (66.67%) and insulin (71.43%) after a 12-day treatment, hence considered to be the most active fraction. Further fractionation of NBF yielded sub-fractions I (SFI) and II (SFII), and only SFI lowered blood glucose (p < 0.05), in IPGTT similar to glibenclamide. The ME, NBF, and SFI correspondingly lowered plasma insulin (p < 0.05) and dose-dependently inhibited glucose transport across isolated rat jejunum implying an extra-pancreatic mechanism. Phytochemical screening showed the presence of flavonoids, terpenes and tannins, in ME, NBF and SFI, and LC-MS analyses revealed 9.52%, 33.30% and 22.50% mangiferin respectively. PM fruit possesses anti-hyperglycemic effect, exerted probably through extra-pancreatic action. Magniferin, contained therein may be responsible for this reported activity.

Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats

Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.

Acute and Sub-Acute Toxicity Evaluation of the Methanolic Extract of Alstonia scholaris Stem Bark

Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD) rats. The methanolic extract of Alstonia scholaris stem bark (ASME) was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg) for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.). Histopathological studies revealed slight degeneration (lesion) and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg). The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged.

Chemical composition, anti-angiogenic and cytotoxicity activities of the essential oils of Cymbopogan citratus (lemon grass) against colorectal and breast carcinoma cell lines

The essential oil of Cymbopogan citratus (lemon grass) was isolated by steam distillation method and subjected to cytotoxicity activity using two different cell lines, human colon carcinoma (HCT-116), breast carcinoma cell lines (MCF-7) and anti-angiogenic activity. The cytotoxicity activity study was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,4-tetrazolium bromide] assay and anti-angiogenic activity using rat aortic ring model. The chemical composition of the essential oil was determined by gas chromatography–mass spectrometry (GC–MS) and GC–flame ionization detection (FID). Forty-one compounds, representing 88.5% of the lemon grass oil was identified and the main components were neral (29.8%) and geranial (44.6%). The free radical scavenging activity of the essential oil showed an IC50 value of 156.1 μg/mL. The results showed that essential oil of lemon grass possessed potential cytotoxic effect on HCT-116 and with the IC50 value of 27.41 ± 4.3 μg/mL comparing to MCF-7 with IC50 value of 41.90 ± 1.2 μg/mL. Significant anti-angiogenic activity of the sample was observed with 99 ± 0.8% of inhibition at 100 μg/mL.

Mechanisms underlying the antihypertensive effect of Alstonia scholaris

ETHNOPHARMACOLOGICAL RELEVANCE Alstonia scholaris has a long history of use in the Ayurveda traditional treatment of various ailments including hypertension. We have reported the blood pressure lowering activity of the extract of A. scholaris. The following research aim to delineate the pharmacological mechanism involve in the antihypertensive action. MATERIALS AND METHOD Vasorelaxant effect of the n-butanol fraction of A. scholaris (NBF-ASME) was evaluated on rat aorta pre-contracted with phenyelphrine (PE, 1 µM). Aortic rings preparation were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ 10 μM), methylene blue (MB 10 μM), Nω-nitro-L-arginine methyl ester hydrochloride (l-NAME 10 μM), atropine (10 μM), indomethacin (1 μM), ML-9 and various K(+) channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study. RESULT The results showed that pre-incubation of aortic rings with the extract (0.5, 1 and 2mg/mL) significantly inhibit the contractile response of the rings to phenylephrine-induced contraction (p<0.05-0.001). Removal of endothelium, incubation with L-NAME, indomethacin, atropine and propranolol did not significantly affect the relaxation effect of NBF-ASME. Furthermore, the K(+) channel blockers, TEA and glibenclamide showed no inhibitory effect. However, aortic rings pretreated with ODQ and ML-9 showed a significant suppression of the relaxation curve of NBF-ASME (p<0.01-0.001). In Ca(2+)-free solution, NBF-ASME inhibits the release of intracellular Ca(2+) from the sarcoplasmic reticulum. NBF-ASME also inhibits calcium chloride (CaCl2)-induced contraction in endothelium-denuded aortic rings. CONCLUSION The results from this study suggests that A. scholaris exerts vasodilation via calcium channels blockade, direct activation of soluble guanylate cyclase and possibly by also inhibiting the formation of inositol 1, 4, 5-triphosphate.

Kigelia africana (Lam.) Benth. (Sausage tree): Phytochemistry and pharmacological review of a quintessential African traditional medicinal plant.

ETHNOPHARMACOLOGICAL RELEVANCE Kigelia africana is a quintessential African herbal medicinal plant with a pan-African distribution and immense indigenous medicinal and non-medicinal applications. The plant is use traditionally as a remedy for numerous disease such as use wounds healing, rheumatism, psoriasis, diarrhea and stomach ailments. It is also use as an aphrodisiac and for skin care. AIM OF THE REVIEW The present review aims to compile an up-to-date review of the progress made in the continuous pharmacological and phytochemistry investigation of K. africana and the corresponding commercial and pharmaceutical application of these findings with the ultimate objective of providing a guide for future research on this plant. METHOD The scholarly information needed for this paper were predominantly sourced from the electronic search engines such as Google, Google scholar; publishing sites such as Elsevier, scienceDirect, BMC, PubMed; other scientific database sites for chemicals such as ChemSpider, PubChem, and also from online books. RESULTS Pharmacological investigations conducted confirm the anti-inflammatory, analgesic, antioxidant and anticancer activity of the extract of different parts of the plant. Bioactive constituents are found to be present in all parts of the plant. So far, approximately 150 compounds have been characterized from different part of the plant. Iridoids, naphthoquinones, flavonoids, terpenes and phenylethanoglycosides are the major class of compounds isolated. Novel compounds with potent antioxidant, antimicrobial and anticancer effect such as verbascoside, verminoside and pinnatal among others, have been identified. Commercial trade of K. africana has boosted in the las few decades. Its effect in the maintenance of skin has been recognized resulting in a handful of skin formulations in the market. CONCLUSIONS The pharmaceutical potentials of K. africana has been recognized and have witness a surge in research interest. However, till date, many of its traditional medicinal uses has not been investigated scientifically. Further probing of the existential researches on its pharmacological activity is recommended with the end-goal of unravelling the pharmacodynamics, pharmacokinetics, clinical relevance and possible toxicity and side effects of both the extract and the active ingredients isolated.

Free Radicals Scavenging Activity, Cytotoxicity and Anti-parasitic Activity of Essential Oil of Psidium guajava L. Leaves against Toxoplasma gondii

Psidium guajava L. (family Myrtaceae), commonly known as guava, is a plant that grows in tropical and subtropical region. Different parts of the plant have been used extensively in traditional folk medicine. In the present study, the essential oil (EO) isolated from guava leaves was investigated for potential antioxidant, in vitro cytotoxicity and in vitro anti-parasitic activity against Toxoplasma gondii parasite. The antioxidant activity was evaluated through DPPH scavenging activity. Guava leaves EO served as a moderate antioxidant, with IC value of 460.56 ± 1.33 µg/mL. The in vitro cytotoxicity activity was investigated using Vero cells, while in vitro anti-parasitic assay was studied using the same cells as host for T. gondii. Growth inhibition was determined using MTT assay. Guava leaves EO was found to be not toxic to Vero cells, with 50 values of 37.54 ± 3.81 µg/mL. In the in vitro anti-T. gondii assay, guava leaves EO showed promising result with EC of 3.94 ± 0.39 µg/mL, as compared to the standard drug clindamycin (EC50 value of 6.24 ± 0.53 µg/mL). In the present study, the potential therapeutic activity of guava leaves EO may have contributed by the in vitro inhibition of free radicals associated with toxoplasmosis pathology.

Mechanism of action of isolated caffeic acid and epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa

Background: The escalating dominance of resistant Pseudomonas aeruginosa strains as infectious pathogen had urged the researchers to look for alternative and complementary drugs. Objective: The objective of this study is to address the biological targets and probable mechanisms of action underlying the potent antibacterial effect of the isolated compounds from Euphorbia hirta (L.) against P. aeruginosa. Materials and Methods: The action mechanisms of caffeic acid (CA) and epicatechin 3-gallate (ECG) on P. aeruginosa cells were investigated by several bacterial physiological manifestations involving outer membrane permeabilization, intracellular potassium ion efflux, and nucleotide leakage. Results: The findings revealed that ECG and CA targeted both cell wall and cytoplasmic membrane of P. aeruginosa. The cellular membrane destruction and ensuing membrane permeability perturbation of P. aeruginosa had led to the ascending access of hydrophobic antibiotics, release of potassium ions, and leakages of nucleotides. Conclusion: The overall study concludes that ECG and CA isolated from E. hirta possess remarkable anti-infective potentials which can be exploited as drug template for the development of new antibacterial agent against resistant P. aeruginosa pathogen. Abbreviations used: ECG: Epicatechin 3-gallate; CA: Caffeic acid; E. hirta: Euphoria hirta.

Antioxidant and cytotoxic effect of Barringtonia racemosa and Hibiscus sabdariffa fruit extracts in MCF-7 human breast cancer cell line

Background: The fruits of Barringtonia racemosa and Hibiscus sabdariffa have been used in the treatment of abscess, ulcer, cough, asthma, and diarrhea as traditional remedy. Objective: This study aims to evaluate cytotoxic effect of B. racemosa and H. sabdariffa methanol fruit extracts toward human breast cancer cell lines (MCF-7) and its antioxidant activities. Materials and Methods: Total antioxidant activities of extracts were assayed using 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) and β-carotene bleaching assay. Content of phytochemicals, total flavonoid content (TFC), and total phenolic content (TPC) were determined using aluminum chloride colorimetric method and Folin-Ciocalteu′s reagent, respectively. Cytotoxic activity in vitro was investigated through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Results: B. racemosa extract exhibited high antioxidant activities compared to H. sabdariffa methanol fruit extracts in DPPH radical scavenging assay (inhibitory concentration [IC 50 ] 15.26 ± 1.25 μg/mL) and ί-carotene bleaching assay (I% 98.13 ± 1.83%). B. racemosa also showed higher TPC (14.70 ± 1.05 mg gallic acid equivalents [GAE]/g) and TFC (130 ± 1.18 mg quercetin equivalents [QE]/g) compared to H. sabdariffa (3.80 ± 2.13 mg GAE/g and 40.75 ± 1.15 mg QE/g, respectively). In MTT assay, B. racemosa extract also showed a higher cytotoxic activity (IC 50 57.61 ± 2.24 μg/mL) compared to H. sabdariffa. Conclusion: The present study indicated that phenolic and flavonoid compounds known for oxidizing activities indicated an important role among the contents of these plants extract. B. racemosa methanol extract have shown potent cytotoxic activity toward MCF-7. Following these promising results, further fractionation of the plant extract is underway to identify important phytochemical bioactives for the development of potential nutraceutical and pharmaceutical use.